Rotavirus outer capsid proteins VP7 and VP4 independently induce the development of protective neutralizing antibodies in the host. Hence, the molecular basis for antigenic differences among VP7s and VP4s is relevant to rotavirus vaccine development. Circulating rotavirus strains from rotavirus vaccine trials were examined by sequence analysis to determine whether antigenic variation plays a role in variable vaccine efficacy that has been observed in several clinical trials. Strains from three different rotavirus vaccine efficacy studies were examined this year: a RRV (serotype 3 VP7) trial in Rochester, New York where protection was observed against a circulating serotype 1 strain; a RRV (serotype 3 VP7) trial in Rochester where protection was not observed against a circulating serotype 1 strain; and an M37 (serotype 1 VP7) study in Finland where protection was not observed against a circulating serotype I strain. Comparison of the VP7 sequences of the strains derived from "vaccine failures" or placebo recipients in these studies with those of the vaccine strain suggest that antigenic variation may play a role in the ability of a circulating strain to escape vaccine-induced immunity. However, additional sequence analysis in concert with examination of the serologic responses of vaccinees will be required to confirm this association.